Reference : The pH dependence of the active-site serine DD-peptidase of Streptomyces R61
Scientific journals : Article
Life sciences : Microbiology
Life sciences : Biochemistry, biophysics & molecular biology
http://hdl.handle.net/2268/81290
The pH dependence of the active-site serine DD-peptidase of Streptomyces R61
English
Varetto, Louis [Université de Liège - ULg > Institut de Chimie > Service de Microbiologie > >]
Frère, Jean-Marie mailto [Université de Liège - ULg > Institut de Chimie > Service de Microbiologie > >]
Nguyen-Distèche, Martine mailto [Université de Liège - ULg > Institut de Chimie > Service de Microbiologie > >]
Ghuysen, Jean-Marie [Université de Liège - ULg > Institut de Chimie > Service de Microbiologie > > >]
Houssier, Claude mailto [Université de Liège - ULg > Institut de Chimie > Laboratoire de Chimie macromoléculaire et Chimie physique > > >]
2-Feb-1987
European Journal of Biochemistry
Blackwell Science
162
3
525-531
Yes (verified by ORBi)
International
0014-2956
1432-1033
Oxford
United Kingdom
[en] acylation ; anti-bacterial agents/pharmacology ; binding sites/drug effects ; carboxypeptidases/antagonists & inhibitors/*metabolism ; hydrogen-ion concentration ; hydrolysis ; kinetics ; lactams ; models, chemical ; oligopeptides/metabolism ; serine-type d-ala-d-ala carboxypeptidase ; streptomyces/*enzymology
[en] Titration of the active-site serine DD-peptidase of Streptomyces R61 shows that formation of acyl enzyme during hydrolysis of the substrate Ac2-L-Lys-D-Ala-D-Ala and enzyme inactivation by the beta-lactam compounds benzylpenicillin, N-acetylampicillin and ampicillin relies on the acidic form of an enzyme's group of pK approximately equal to 9.5. It is proposed that protonation of a lysine epsilon-amino group facilitates initial binding by charge pairing with the free carboxylate of the substrate and the beta-lactam molecules. Lowering the pH from 7 to 5 has no effect on the second-order rate constant of enzyme acylation by benzylpenicillin and N-acetylampicillin but results in a decreased rate constant of acylation by ampicillin and Ac2-L-Lys-D-Ala-D-Ala. Protonation of the side-chain amino group of ampicillin and a decreased efficacy of the initial binding of the peptide to the enzyme seem to be responsible for the observed effects. Whatever the molecule bound to the enzyme, there is no sign for the active involvement of an enzyme's histidine residue of pK 6.5-7.0 in the hydrolysis pathway.
Researchers ; Professionals
http://hdl.handle.net/2268/81290

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